Nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs): These include medications such as zidovudine (AZT/Retrovir), didanosine (ddI/Videx), stavudine (d4T/Zerit), lamivudine (3TC/Epivir), abacavir (ABC/Ziagen), emtricitabine (FTC/Emtriva), tenofovir (TDF/Viread), and tenofovir alafenamide (TAF).
HIV is the virus that’s passed from person to person. Over time, HIV destroys an important kind of the cell in your immune system (called CD4 cells or T cells) that helps protect you from infections. When you don’t have enough of these CD4 cells, your body can’t fight off infections the way it normally can.
The ability of cytotoxic T lymphocytes to destroy HIV-infected cells is demonstrated by studies of peripheral blood cells from infected individuals, in which cytotoxic T cells specific for viral peptides can be shown to kill infected cells in vitro. In vivo, cytotoxic T cells can be seen to invade sites of HIV replication and they could, in theory, be responsible for killing many productively infected cells before any infectious virus can be released, thereby containing viral load at the quasi-stable levels that are characteristic of the asymptomatic period. The best evidence for the clinical importance of the control of HIV-infected cells by CD8 cytotoxic T cells comes from studies relating the numbers and activity of CD8 T cells to viral load. An inverse correlation was found between the number of CD8 T cells carrying a receptor specific for an HLA-A2-restricted HIV peptide and plasma RNA viral load. Similarly, patients with high levels of HIV-specific CD8 T cells showed slower progression of disease than those with low levels. There is also direct evidence from experiments in macaques infected with simian immunodeficiency virus (SIV) that CD8 cytotoxic T cells control retrovirally-infected cells in vivo. Treatment of infected animals with depleting anti-CD8 monoclonal antibodies was followed by a large increase in viral load.
A small but vocal minority of people, including some scientists, continue to argue that HIV does not exist, or does not cause AIDS, and that the HIV tests are unreliable or that the therapies are toxic. Such misinformation is usually based on a lack of understanding of the scientific literature, deliberate misrepresentation, or logical fallacies based on pseudoscientific arguments.
Adapted from the World Health Organization: Guidelines on postexposure prophylaxis for HIV and the use of co-trimoxazole prophylaxis for HIV-related infections among adults, adolescents and children: Recommendations for a public health approach—December 2014 supplement to the 2013 consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. Available at http://www.who.int/hiv/pub/guidelines/arv2013/arvs2013upplement_dec2014/en/.
acute compartment syndrome; ACS increased lower-limb intracompartmental pressure on exercise (exercise expands muscles, increases intracompartmental pressures, inducing pain); treated initially by rest, immobilization, non-steroidal anti-inflammatory drugs; severe cases may require surgical decompression (fasciotomy)
Human immunodeficiency virus infection and AIDs can cause a plethora of hematologic problems. Early on during HIV infection, immune thrombocytopenia is common as is the development of antiphospholipid antibodies. Anemia is the most common manifestation of HIV infection and is multifactorial due to both direct and indirect effects of the virus.12 Anemia is most often a hypoproliferative, low reticulocyte anemia due to anemia of chronic disease. Often, there is a blunted erythropoietin response. Coombs-positive autoimmune hemolytic anemia also occurs with increased frequency in HIV infection. Antiretroviral therapy often causes macrocytosis.
Patients with late-stage AIDS may develop Kaposi’s sarcoma (KS), a skin tumor that primarily affects homosexual men. KS is the most common AIDS-related malignancy. It is characterized by reddish-purple blotches or patches (brownish in people with dark skin) on the skin or in the mouth. About 40% of patients with KS develop symptoms in the digestive tract or lungs. KS may be caused by a herpes virus-like sexually transmitted disease agent rather than HIV.
When CD4 T-cell numbers decline below a critical level, cell-mediated immunity is lost, and infections with a variety of opportunistic microbes appear (Fig. 11.29). Typically, resistance is lost early to oral Candida species and to Mycobacterium tuberculosis, which shows as an increased prevalence of thrush (oral candidiasis) and tuberculosis. Later, patients suffer from shingles, caused by the activation of latent herpes zoster, from EBV-induced B-cell lymphomas, and from Kaposi’s sarcoma, a tumor of endothelial cells that probably represents a response both to cytokines produced in the infection and to a novel herpes virus called HHV-8 that was identified in these lesions. Pneumonia caused by the fungus Pneumocystis carinii is common and often fatal. In the final stages of AIDS, infection with cytomegalovirus or Mycobacterium avium complex is more prominent. It is important to note that not all patients with AIDS get all these infections or tumors, and there are other tumors and infections that are less prominent but still significant. Rather, this is a list of the commonest opportunistic infections and tumors, most of which are normally controlled by robust CD4 T cell-mediated immunity that wanes as the CD4 T-cell counts drop toward zero (see Fig. 11.21).
[Guideline] Günthard HF, Aberg JA, Eron JJ, for the International Antiviral Society-USA Panel. Antiretroviral treatment of adult HIV infection: 2014 recommendations of the International Antiviral Society-USA Panel. JAMA. 2014 Jul 23-30. 312(4):410-25. [Medline]. [Full Text].
In considering disclosure, clinicians may have competing obligations: protecting the patient’s confidentiality, on the one hand, and disclosing test results to prevent substantial harm to a third party, on the other. In some jurisdictions, a breach of confidentiality may be required by mandatory reporting regulations. Even absent legal requirements, in some situations the need to protect potentially exposed third parties may seem compelling. In these situations, the clinician first should educate the patient about her rights and responsibilities and encourage her to inform any third parties involved. If she remains reluctant to voluntarily share information regarding her infection, consultation with an institutional ethics committee, a medical ethics specialist, or an attorney may be helpful in deciding whether to disclose her HIV status. In general, a breach of confidentiality may be ethically justified for purposes of partner notification when all of the following four conditions are met:
Stein-Leventhal syndrome; polycystic ovary syndrome multiple ovarian cyst formation, with associated menstrual abnormalities, infertility, enlarged ovaries, insulin resistance, obesity, acne, evidence of masculinization (e.g. hirsuitism) and increased tendency to type 2 diabetes mellitus; responds to treatment with oral contraceptive pill and/or metformin
In 2003, President george w. bush proposed spending $15 billion over five years to support international AIDS prevention and the purchase of anti-viral drugs. The largest share of the money would be contributed directly by the United States to other countries, such as through programs sponsored by the U.S. Agency for International Development. The proposal would account for almost half the money in a global fund committed to fight HIV and AIDS.
In February 1987, the WHO launched The Global Program on AIDS to raise awareness; generate evidence-based policies; provide technical and financial support to countries; conduct research; promote participation by NGOs; and promote the rights of people living with HIV.36
For this strategy to work, however, one must be able to test people at risk of infection with HIV periodically, so that they can take the steps necessary to avoid passing the virus to others. This, in turn, requires strict confidentiality and mutual trust. A barrier to the control of HIV is the reluctance of individuals to find out whether they are infected, especially as one of the consequences of a positive HIV test is stigmatization by society. As a result, infected individuals can unwittingly infect many others. Balanced against this is the success of therapy with combinations of the new protease inhibitors and reverse transcriptase inhibitors, which provides an incentive for potentially infected people to identify the presence of infection and gain the benefits of treatment. Responsibility is at the heart of AIDS prevention, and a law guaranteeing the rights of people infected with HIV might go a long way to encouraging responsible behavior. The rights of HIV-infected people are protected in the Netherlands and Sweden. The problem in the less-developed nations, where elementary health precautions are extremely difficult to establish, is more profound.
Oral PrEP of HIV is the daily use of ARV drugs by HIV-negative people to block the acquisition of HIV. More than 10 randomized controlled studies have demonstrated the effectiveness of PrEP in reducing HIV transmission among a range of populations including serodiscordant heterosexual couples (where one partner is infected and the other is not), men who have sex with men, transgender women, high-risk heterosexual couples, and people who inject drugs.
Jump up ^ Thorley JA, McKeating JA, Rappoport JZ (2010). “Mechanis ms of viral entry: sneaking in the front door”. Protoplasma. 244 (1–4): 15–24. doi:10.1007/s00709-010-0152-6. PMC 3038234 . PMID 20446005.
DDI also causes pancreatitis and, to a lesser extent, peripheral neuropathy. Peripheral neuropathy can become permanent and painful, and pancreatitis can be life-threatening if therapy is not discontinued. The drug ddC also is associated with peripheral neuropathy, as well as oral ulcers.
The main cellular target of HIV is a special class of white blood cells critical to the immune system known as helper T lymphocytes, or helper T cells. Helper T cells are also called CD4+ T cells, because they have on their surfaces a protein called CD4. Helper T cells play a central role in normal immune responses by producing factors that activate virtually all the other immune system cells. Those include B lymphocytes, which produce antibodies needed to fight infection; cytotoxic T lymphocytes, which kill cells infected with a virus; and macrophages and other effector cells, which attack invading pathogens. AIDS results from the loss of most of the helper T cells in the body.
Shortly after the viral capsid enters the cell, an enzyme called reverse transcriptase liberates the positive-sense single-stranded RNA genome from the attached viral proteins and copies it into a complementary DNA (cDNA) molecule. The process of reverse transcription is extremely error-prone, and the resulting mutations may cause drug resistance or allow the virus to evade the body’s immune system. The reverse transcriptase also has ribonuclease activity that degrades the viral RNA during the synthesis of cDNA, as well as DNA-dependent DNA polymerase activity that creates a sense DNA from the antisense cDNA. Together, the cDNA and its complement form a double-stranded viral DNA that is then transported into the cell nucleus. The integration of the viral DNA into the host cell’s genome is carried out by another viral enzyme called integrase.
Jump up ^ Crispin, Max; Doores, Katie J (2015). “Targeting host-derived glycans on enveloped viruses for antibody-based vaccine design”. Current Opinion in Virology. 11: 63–9. doi:10.1016/j.coviro.2015.02.002. PMC 4827424 . PMID 25747313.
Avoid exposure to blood from injuries or nosebleeds where the HIV status of the bleeding individual is unknown. Protective clothing, masks, and goggles may be appropriate when caring for people who are injured.
AIDS is an acquired immunodeficiency syndrome defined by a severe depletion of T cells and over 20 conventional degenerative and neoplastic diseases. In the U.S. and Europe, AIDS correlates to 95% with risk factors, such as about 8 years of promiscuous male homosexuality, intravenous drug use, or hemophilia. Since AIDS also correlates with antibody to a retrovirus, confirmed in about 40% of American cases, it has been hypothesized that this virus causes AIDS by killing T cells. Consequently, the virus was termed human immunodeficiency virus (HIV), and antibody to HIV became part of the definition of AIDS. The hypothesis that HIV causes AIDS is examined in terms of Koch’s postulates and epidemiological, biochemical, genetic, and evolutionary conditions of viral pathology. HIV does not fulfill Koch’s postulates: (i) free virus is not detectable in most cases of AIDS; (ii) virus can only be isolated by reactivating virus in vitro from a few latently infected lymphocytes among millions of uninfected ones; (iii) pure HIV does not cause AIDS upon experimental infection of chimpanzees or accidental infection of healthy humans. Further, HIV violates classical conditions of viral pathology. (i) Epidemiological surveys indicate that the annual incidence of AIDS among antibody-positive persons varies from nearly 0 to over 10%, depending critically on nonviral risk factors. (ii) HIV is expressed in less than or equal to 1 of every 10(4) T cells it supposedly kills in AIDS, whereas about 5% of all T cells are regenerated during the 2 days it takes the virus to infect a cell. (iii) If HIV were the cause of AIDS, it would be the first virus to cause a disease only after the onset of antiviral immunity, as detected by a positive “AIDS test.” (iv) AIDS follows the onset of antiviral immunity only after long and unpredictable asymptomatic intervals averaging 8 years, although HIV replicates within 1 to 2 days and induces immunity within 1 to 2 months. (v) HIV supposedly causes AIDS by killing T cells, although retroviruses can only replicate in viable cells. In fact, infected T cells grown in culture continue to divide. (vi) HIV is isogenic with all other retroviruses and does not express a late, AIDS-specific gene. (vii) If HIV were to cause AIDS, it would have a paradoxical, country-specific pathology, causing over 90% Pneumocystis pneumonia and Kaposi sarcoma in the U.S. but over 90% slim disease, fever, and diarrhea in Africa.(viii) It is highly improbable that within the last few years two viruses (HIV-1 and HIV-2) that are only 40% sequence-related would have evolved that could both cause the newly defined syndrome AIDS. Also, viruses are improbable that kill their only natural host with efficiencies of 50-100%, as is claimed for HIVs. It is concluded that HIV is not sufficient for AIDS and that it may not even be necessary for AIDS because its activity is just as low in symptomatic carriers as in asymptomatic carriers. The correlation between to HIV and AIDS does not prove causation, because otherwise indistinguishable diseases are now set apart only on the basis of this antibody. I propose that AIDS is not a contagious syndrome caused by one conventional virus or microbe. No such virus or microbe would require almost a decade to cause primary disease, nor could it cause the diverse collection of AIDS diseases. Neither would its host range be as selective as that of AIDS, nor could it survive if it were as inefficiently transmitted as AIDS. Since AIDS is defined by new combinations of conventional diseases, it may be caused by new combinations of conventional pathogens, including acute viral or microbial infections and chronic drug use and malnutrition. The long and unpredictable intervals between infection with HIV and AIDS would then reflect the thresholds for these pathogenic factors to cause AIDS diseases, instead of an unlikely mechanism of HIV pathogenesis.
HIV may be the human version of simian immunodeficiency virus (SIV), known to infect African chimpanzees. It may have crossed over and mutated in humans who ate infected chimpanzee meat as long ago as the late 1800s.
Most people infected with HIV develop specific antibodies (i.e. seroconvert) within three to twelve weeks of the initial infection. Diagnosis of primary HIV before seroconversion is done by measuring HIV-RNA or p24 antigen. Positive results obtained by antibody or PCR testing are confirmed either by a different antibody or by PCR. [redirect url=’http://penetratearticles.info/bump’ sec=’7′]