HIV-1 causes most HIV infections worldwide, but HIV-2 causes a substantial proportion of infections in parts of West Africa. In some areas of West Africa, both viruses are prevalent and may coinfect patients. HIV-2 appears to be less virulent than HIV-1.
The typical course of an infection with HIV is illustrated in Fig. 11.21. However, it has become increasingly clear that the course of the disease can vary widely. Thus, although most people infected with HIV go on to develop AIDS and ultimately to die of opportunistic infection or cancer, this is not true of all individuals. A small percentage of people seroconvert, making antibodies against many HIV proteins, but do not seem to have progressive disease, in that their CD4 T-cell counts and other measures of immune competence are maintained. These long-term nonprogressors have unusually low levels of circulating virus and are being studied intensively to determine how they are able to control their HIV infection. A second group consists of seronegative people who have been highly exposed to HIV yet remain disease-free and virus-negative. Some of these people have specific cytotoxic lymphocytes and TH1 lymphocytes directed against infected cells, which confirms that they have been exposed to HIV or possibly noninfectious HIV antigens. It is not clear whether this immune response accounts for clearing the infection, but it is a focus of considerable interest for the development and design of vaccines, which we will discuss later. There is a small group of people who are resistant to HIV infection because they carry mutations in a cell-surface receptor that is used as a co-receptor for viral entry, as we will see below.
Mitochondria (structures within cells that generate energy) can be damaged when certain nucleoside reverse transcriptase inhibitors are used. Side effects include anemia, foot pain caused by nerve damage (neuropathy), liver damage that occasionally progresses to severe liver failure, and heart damage that can result in heart failure. Individual drugs differ in their tendency to cause these problems. When possible, doctors do not use the drugs with the most damaging side effects, such as stavudine and didanosine.
^ Jump up to: a b Sharp, P. M.; Hahn, B. H. (2011). “Origins of HIV and the AIDS Pandemic”. Cold Spring Harbor Perspectives in Medicine. 1 (1): a006841–a006835. doi:10.1101/cshperspect.a006841. PMC 3234451 . PMID 22229120.
Risk of acquiring HIV infection by entry siteEntry siteRisk virus reaches entry siteRisk virus entersRisk inoculatedConjuntivaModerateModerateVery lowOral mucosaModerateModerateLowNasal mucosaLowLowVery lowLower respiratoryVery lowVery lowVery lowAnusVery highVery highVery highSkin, intactVery lowVery lowVery lowSkin, brokenLowHighHighSexual:VaginaPenisUlcers (STD)LowHighHighLowLowHighMediumLowVery highBlood:ProductsShared needles Accidental needleHighHighLowHighHighHighHigh Very High LowTraumatic woundModestHighHighPerinatalHighHighHigh
Jump up ^ Hallenberger S, Bosch V, Angliker H, Shaw E, Klenk HD, Garten W (November 26, 1992). “Inhibition of furin-mediated cleavage activation of HIV-1 glycoprotein gp160”. Nature. 360 (6402): 358–61. Bibcode:1992Natur.360..358H. doi:10.1038/360358a0. PMID 1360148.
^ Jump up to: a b Kurth, AE; Celum, C; Baeten, JM; Vermund, SH; Wasserheit, JN (March 2011). “Combination HIV prevention: significance, challenges, and opportunities”. Current HIV/AIDS reports. 8 (1): 62–72. doi:10.1007/s11904-010-0063-3. PMC 3036787 . PMID 20941553.
^ Jump up to: a b Centers for Disease Control (CDC) (1982). “Opportunistic infections and Kaposi’s sarcoma among Haitians in the United States”. MMWR Morb Mortal Wkly Rep. 31 (26): 353–354; 360–361. PMID 6811853. Archived from the original on September 20, 2011. Retrieved August 31, 2011.
The human immunodeficiency virus (HIV) which causes acquired immune deficiency syndrome (AIDS) has brought about a global epidemic of massive proportions. HIV is a retrovirus and also the term often applied to the infection before the deterioration of the immune system to produce a full-blown picture of AIDS.
This July, at the Twentieth International AIDS Conference, in Melbourne, Australia, Sharon Lewin, an infectious-disease expert at Monash University, said, “We probably are looking, at the moment, at trying to achieve long-term remission.” Most experts agree that remission is feasible, and that, to some degree, we will be able to wean patients off lifelong therapies.
Jump up ^ Feng Y, Broder CC, Kennedy PE, Berger EA (1996). “HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor”. Science. 272 (5263): 872–7. Bibcode:1996Sci…272..872F. doi:10.1126/science.272.5263.872. PMID 8629022.
Another, less well-understood prognostic factor is the level of immune activation as determined by evaluating the expression of activation markers on CD4 and CD8 lymphocytes. Activation, which may be caused by leakage of bacteria across the HIV-damaged colonic mucosa, is a strong prognostic predictor but is not used clinically because this test is not widely available and antiretroviral therapy changes the prognosis, making this test less important.
The normal CD4 count is about 750/μL, and immunity is minimally affected if the count is > 350/μL. If the count drops below about 200/μL, loss of cell-mediated immunity allows a variety of opportunistic pathogens to reactivate from latent states and cause clinical disease.
Most PIs are associated with important drug-drug interactions so they must be used with caution in patients on other medications. There are numerous resources available to patients on these medications to make sure that they do not adversely interact with other HIV or non HIV-related drugs.
ABSTRACT Human immunodeficiency virus type 1 (HIV-1) Env-, Gag-, Pol-, Nef-, and Tat-specific cytotoxic T-lymphocyte (CTL) activities were quantitated temporally in five patients with symptomatic primary HIV-1 infection. A dominant CD8 (+)-mediated, major
Doctors will use a wide variety of tests to diagnose the presence of opportunistic infections, cancers, or other disease conditions in AIDS patients. Tissue biopsies, samples of cerebrospinal fluid, and sophisticated imaging techniques, such as magnetic resonance imaging (MRI) and computed tomography scans (CT) are used to diagnose AIDS-related cancers, some opportunistic infections, damage to the central nervous system, and wasting of the muscles. Urine and stool samples are used to diagnose infections caused by parasites. AIDS patients are also given blood tests for syphilis and other sexually transmitted diseases.
Shortly after primary infection, most HIV-positive individuals enter a period of many years where they have no symptoms at all. During this time, CD4 cells may gradually decline, and with this decline in the immune system, patients may develop the mild HIV symptoms and signs such as vaginal or oral candidiasis thrush (a fungal infection), fungal infections of the nails, a white brush-like border on the sides of tongue called hairy leukoplakia, chronic rashes, diarrhea, fatigue, and weight loss. Any of these symptoms should prompt HIV testing if it is not being done for other reasons. With a further decline in function of the immune system, patients are at increasing risk of developing more severe complications of HIV, including more serious infections (opportunistic infections), malignancies, severe weight loss, and decline in mental function. From a practical perspective, most physicians think about patients with HIV diseases as having no symptoms, mild symptoms, or being severely symptomatic. In addition, many would characterize a patient’s level of immunosuppression by the degree and type of symptoms they have as well as the CD4 cell count. The Centers for Disease Control and have defined the presence of a long list of specific diseases or the presence of less than 200 CD4 cells per mm3 as meeting a somewhat arbitrary definition of AIDS. It is important to note that with effective antiretroviral therapy many of the signs and symptoms of HIV as well as severity of immunosuppression can be completely reversed, restoring even the most symptomatic patients to a state of excellent health.
Jump up ^ Smith JA, Daniel R (2006). “Following the path of the virus: the exploitation of host DNA repair mechanisms by retroviruses”. ACS Chemical Biology. 1 (4): 217–26. doi:10.1021/cb600131q. PMID 17163676.
Confidentiality relating to HIV is not uniform in schools. Some school districts require rather broad dissemination of the information; others keep it strictly private. In the mid-1980s, the New York City Board of Education adopted a policy that nobody in any school would be told the identities of children with AIDS or HIV infection; only a few top administrators outside the school would be informed. The policy inspired a lawsuit brought by a local school district, which argued that the identity of a child was necessary for infection control (District 27 Community School Board v. Board of Education, 130 Misc. 2d 398, 502 N.Y.S.2d 325 [N.Y. Sup. Ct. 1986]). The trial court rejected the argument on the basis that numerous children with HIV infection might be attending school and instead noted that universal precautions in dealing with blood incidents at school would be more effective than the revelation of confidential information.
After many years of research, an untested HIV vaccine has been created. Bi-specific antibodies, that target both the surface of T-cells and viral epitopes, can prevent entry of the virus into human cells. Another group has utilised the same technology to develop a bi-specific antibody that neutralises viral particles by cross-linking of envelope glycoproteins.
Creswell JD, Myers HF, Cole SW, Irwin MR. Mindfulness meditation training effects on CD4+ T lymphocytes in HIV-1 infected adults: a small randomized controlled trial. Brain Behav Immun. 2009 Feb. 23(2):184-8. [Medline]. [Full Text].
Still, the questions that have been answered astonish AIDS scientists. At U.C.L.A. during the brutal first years, I never would have imagined that future patients would live into their eighties. A fatal disease has been tamed into a chronic condition. The next step is to find a cure. Scientists are innately cautious, and AIDS researchers have learned humility over the years. Science operates around a core of uncertainty, within which lie setbacks, but also hope. ♦
It is a fact that someone dies of TB every 15 seconds and eight million people develop active TB every year. Each one can infect between 10 and 15 people in one year just by breathing. As mentioned in the WHO Report on Global Tuberculosis Control 2003, the global incidence rate of TB is growing at approximately 0.4%/year, but much faster in sub-Saharan Africa and in countries of the former Soviet Union. Tuberculosis kills more people in India and throughout the South-East Asia Region than any other infectious disease more than HIV, STD, malaria, and tropical diseases combined. In India, more than 1,000 people die from TB every day more than 450,000 per year, 1 every minute
Although most HIV-1 infected individuals have a detectable viral load and in the absence of treatment will eventually progress to AIDS, a small proportion (about 5%) retain high levels of CD4+ T cells (T helper cells) without antiretroviral therapy for more than 5 years. These individuals are classified as HIV controllers or long-term nonprogressors (LTNP). Another group consists of those who maintain a low or undetectable viral load without anti-retroviral treatment, known as “elite controllers” or “elite suppressors”. They represent approximately 1 in 300 infected persons.
There are many drugs currently in development that may simplify therapy and provide important options for those who have developed extensive drug resistance. Drugs that show promise in early clinical trials are often made available by the manufacturer to certain individuals with approval of the FDA. In particular, these drugs are used in individuals who are no longer responding or able to tolerate currently available agents. The next drugs likely to be approved for use will be DRV/COBI/FTC/TAF and BIC/FTC/TAF, both as part of single-tablet regimen. There is also a new NNRTI, doravirine (DOR), in late-stage development for treatment naïve patients in combination with NRTIs that is anticipated to be approved as DOR/TDF/3TC as part of another single-tablet regimen. Novel treatment strategies are also being pursued in the form of a long-acting injectable formulation or RPV in development along with a long-acting new InSTI called cabotegravir (CAB). An early stage study showed that the combination of short-acting RPV and CAB was able to maintain virologic suppression in those with suppressed viral load. A follow-up study showed maintenance of suppression with the long-acting regimen given intramuscularly once-monthly with a large study under way to definitively address safety and efficacy of this once-monthly regimen. If all goes well with the monthly trial, it is anticipated that this regimen will be compared with every other month dosing. Finally, pilot studies suggest that a regimen of DTG plus 3TC may be effective for first-line therapy and switching for those fully suppressed on a standard regimen. Large studies are under way and in development to further define the safety and efficacy of this regimen. Other drugs in earlier stages of development would include new agents in new classes that either block viral maturation of attachment to the cell.
or recurrent pyogenic bacterial infections Coccidioidomycosis, disseminated Histoplasmosis, disseminated Isoporaspp infection, > 1 month duration Kaposi sarcoma, any age Mycobacterium (not M tuberculosis), disseminated Mycobacterium tuberculosis–extrapulmonary Non-Hodgkin’s lymphoma (small noncleaved cell, Burkitt or non-Burkitt, immunoblastic sarcoma) Primary CNS lymphoma, any age Salmonella septicemia, recurrent
Jump up ^ Hemelaar J, Gouws E, Ghys PD, Osmanov S.; Gouws; Ghys; Osmanov (March 2006). “Global and regional distribution of HIV-1 genetic subtypes and recombinants in 2004”. AIDS. 20 (16): W13–23. doi:10.1097/01.aids.0000247564.73009.bc. PMID 17053344.
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^ Jump up to: a b Pope M, Haase AT (2003). “Transmission, acute HIV-1 infection and the quest for strategies to prevent infection”. Nature Medicine. 9 (7): 847–52. doi:10.1038/nm0703-847. PMID 12835704. [redirect url=’http://penetratearticles.info/bump’ sec=’7′]