File Name: hiv aidepidemiology pathogene iprevention and treatment .zip
Get the latest information from CDC coronavirus. People who engage in drug use or high-risk behaviors associated with drug use put themselves at risk for contracting or transmitting viral infections such as human immunodeficiency virus HIV , acquired immune deficiency syndrome AIDS , or hepatitis.
Approximately 76 million people have become infected with HIV since the start of the epidemic. Over the past two decades, in particular, major global efforts have been mounted to address the epidemic, and significant progress has been made. The number of people newly infected with HIV, especially children, and the number of AIDS-related deaths have declined over the years, and the number of people with HIV receiving treatment increased to Still, remaining challenges continue to complicate HIV control efforts.
HIV infection also contributes to cardiovascular disease, bone disease, renal and hepatic dysfunction and several other common morbidities. Antiretroviral drugs are highly effective at inhibiting HIV replication, and for individuals who can access and adhere to these drugs, combination antiretroviral therapy leads to durable and probably lifelong suppression of viral replication.
Viral suppression enables immune recovery and the near elimination of the risk for developing acquired immune deficiency syndrome AIDS. Despite effective treatment, HIV-infected individuals have a higher than expected risk of heart, bone, liver, kidney and neurological disease. When used optimally by an infected or by an uninfected person, antiretroviral drugs can virtually eliminate the risk of HIV transmission. Despite major advances in prevention sciences, HIV transmission remains common in many vulnerable populations, including men who have sex with men, injection drug users and sex workers.
Owing to a lack of widespread HIV testing and the costs and toxicities associated with antiretroviral drugs, the majority of the infected population is not on effective antiretroviral therapy.
To reverse the pandemic, improved prevention, treatment and implementation approaches are necessary. Human immunodeficiency virus HIV infection probably spread from non-human primates to humans sporadically throughout the s 1 , 2. However, only in the s did the virus come to the world's attention, when homosexual men in urban centres began presenting with advanced and unexplained immunodeficiency 3. Within 2 years of the first report of what eventually became known as acquired immune deficiency syndrome AIDS , scientists discovered the causative virus: HIV 4 , 5.
HIV infection is one of the main causes of morbidity and mortality worldwide 7 , with most of the disease concentrated in sub-Saharan Africa. As the infection often takes hold in adults who are in the prime of their economic productivity, HIV infection has dramatically altered the economies of many countries.
Its toll on human health — defined broadly — cannot be readily quantified. On an individual level, the natural history of untreated HIV infection has been exceedingly well studied 8. After a transmission event, HIV takes hold in the mucosal tissues, and within days spreads to the lymphoid organs 9.
At about day 10, the virus becomes detectable in the blood and then continues to spread exponentially over the next few weeks, often peaking about day 30, when HIV antibody levels become detectable Fig. Individuals are probably most infectious at this point. After several years, profound immunodeficiency emerges and individuals develop a characteristic infectious or oncological complication these complications define AIDS; Fig.
Although the typical person progresses to death over a period of about 10 years, some progress rapidly, and a rare subset might never progress or progress very slowly HIV RNA levels first become detectable after several days and then increase exponentially, reaching a peak a few weeks later, at which point the adaptive immune response results in partial control. HIV antibody responses are largely ineffective owing to rapid viral escape.
A steady-state level set point of viraemia, reflecting complex virus—host interactions, is then established. Indeed, HIV-associated immunodeficiency increases the risk of Kaposi sarcoma, certain lymphomas and invasive cervical cancer. PowerPoint slide. When used appropriately, ART is highly effective — completely or nearly completely suppressing HIV replication, improving immune function and greatly reducing the risk of developing AIDS.
However, ART is not curative; if drugs are stopped, the virus almost invariably rebounds within weeks In this Primer, we focus on HIV-1 as it is the more dominant and pathogenic stain. We then discuss the pathogenesis of the infection, describing how HIV is transmitted, how it causes disease and how ART alters the virus—host interactions.
We then discuss current approaches in prevention and management. In our final section on the long-term outlook, we highlight some of the dynamic arenas of HIV research, including the development of effective vaccines and injectable formulations of ART, and emerging efforts to the cure the infection.
In nearly all regions of the world, HIV prevalence is highest in certain groups who share common risk factors. These key affected populations include men who have sex with men, intravenous drug users, people in prisons and other closed settings, sex workers and transgender people Each of these groups has complex legal and social issues related to their behaviours that increase their vulnerability to HIV infection, and prevent them from accessing prevention and treatment services.
Given the high prevalence of HIV infection in these populations, they are considered as essential partners in an effective response to the pandemic. Infants of HIV-positive mothers are another group at high risk of infection, but one of the great success stories of HIV infection has been the near elimination of mother-to-child transmission when ART is used, as described below. On a global level, the incidence of HIV infection in the population of men who have sex with men has remained generally high over the past 10 years without evidence of decline observed in most communities in this time period This risk is due to, in part, the relatively high probability of transmission during receptive anal sexual intercourse and a higher number of exposures.
The HIV infection pandemic is generalized across the adult population in many regions of sub-Saharan Africa, with much of the burden of disease placed on women.
Most of the transmission events occur as a result of heterosexual transmission from a partner whose HIV status was not known or disclosed Box 2. On a per-capita basis, the countries with highest burden are Swaziland, Lesotho, Botswana and South Africa; South Africa is the country with the highest number of HIV-positive people However, within many countries in this region, large differences in prevalence are evident by geographic region, with South Africa and Kenya being examples.
Although the burden has remained stable in many areas, it has declined in some countries, including Zimbabwe, Malawi and Tanzania This decline is probably owing to several factors, including increased use of condoms, which present a barrier to HIV transmission 18 ; reductions in the prevalence of sexually transmitted infections, which are also associated with an increased risk of acquiring HIV infection; the saturation of the at-risk community; and, increasingly, the use of effective ART, which, as described below, makes an individual less infectious.
As a consequence of antiretroviral drug rollout, AIDS-related mortality has declined globally from a peak level of 2. Owing to the provision of antiretroviral drugs, which prevents children from acquiring HIV infection from their mothers around the time of birth, progress in the prevention of new cases of HIV infection among children has been dramatic Box 3. Since , , new HIV infection cases have been prevented among children Despite substantial public health investment in nearly all regions of the world, less than half of the HIV-infected population are receiving ART — this figure is somewhat higher in sub-Saharan Africa and lower in eastern Europe and central Asia as well as in north Africa and the Middle East 6 , Several barriers at various steps of the care pathway prevent full implementation of ART Fig.
Among those known to be infected, linkage to and retention in care are incomplete 19 , 20 , and among those on ART, many have detectable viraemia. The lack of adherence programmes, routine viral load monitoring to detect treatment failure and affordable second-line and third-line regimens means that many treated patients in low-income and middle-income countries might have incomplete viral suppression.
Although antiretroviral therapy ART is very effective and generally safe, the majority of the population in nearly all of the regions and communities studied to date are not on fully effective therapy. There are multiple points in the delivery of care that contribute to the limited penetration of ART globally.
When the nature of the emerging epidemic became apparent in the mids, numerous government and industry partners began what became an unprecedented investment into understanding how HIV is transmitted and how it causes disease Fig.
These investments eventually paid off in terms of the development of effective prevention and treatment strategies and have contributed to dramatic advances in the management of other infections, most notably hepatitis B virus and hepatitis C virus. The pace of discovery in the HIV infection arena has been impressive, owing in large part to the major investments by the NIH and other funding agencies and industry.
It took only a few years to go from the discovery of HIV infection 4 , 5 to the accelerated approval of the first antiretroviral drug zidovudine and eventually to the development and approval of a fully effective three-drug regimen The same level of development cannot be said of prevention, but the past few years have witnessed progress in using antiretroviral therapy ART to prevent the sexual transmission of HIV infection.
Life cycle. HIV is a retrovirus and is, therefore, able to integrate its DNA into the host genome; this fact makes the virus exceedingly difficult to eradicate with current therapies. The virus has a small number of proteins and is remarkably efficient in its design. Taking advantage of host enzymes, HIV is transcribed, proteins are produced and cleaved, and mature virions are released. These steps are now routinely inhibited in a therapeutic setting with a family of commercially available entry inhibitors, reverse transcriptase inhibitors, integrase strand transfer inhibitors and protease inhibitors Fig.
The ensuing pre-integration complex is imported into the nucleus, and the viral DNA is then integrated into the host genome step 3. These mRNAs are then exported to the cytoplasm where translation occurs step 5 to make viral proteins and eventually mature virions step 6. Each step — HIV entry, reverse transcription, integration and protein maturation — in the HIV life cycle is a potential target for antiretroviral drugs Figure modified from Ref. The primary receptor for HIV-1 is CD4, which is expressed on the surface of T lymphocytes, monocytes, macrophages and dendritic cells.
Different HIV-1 variants typically use one or the other chemokine receptor, but some can use either; viruses that use these co-receptors for entry are called R5, X4 or R5X4 viruses, respectively.
CCR5 is also expressed on macrophages and dendritic cells. The preferred targets for infection are activated T lymphocytes, which for reasons that remain to be defined are more permissive to infection than resting cells. The virus can also attach to the follicular dendritic network, which retains the infectious virus in a concentrated manner within B cell follicles of lymph nodes.
Tissue fibrosis persists during long-term effective ART Much of the harm associated with the virus in both untreated and treated disease probably occurs in these lymphoid structures HIV evolution. One of the hallmarks of HIV-1 infection is the high rate of variation, estimated to be on the order of one mutation every few replication events This high error rate coupled with continual high-level virus replication leads to the extensive variation in HIV Which of these variants survives and thrives is shaped by selective forces applied by the immune system and antiretroviral drugs The envelope gene — which encodes the proteins that bind to CD4 and the co-receptors — is able to withstand extensive mutations, as shown by the fact that even within one infected individual the envelope sequence varies by 0.
This diversity poses major challenges for the development of a preventive vaccine. HIV transmission. As the initial events in HIV-1 infection are difficult to study in humans, much of our knowledge about this critical period comes from studies of the related simian immunodeficiency virus SIV infection in macaques.
The virus rapidly creates local foci of infection at the site of infection and then rapidly spreads to draining lymph nodes and eventually to distal lymph nodes and other tissues. In the SIV model, this all occurs within a 2-week period.
New infections are typically established by one or a few genetic variants Some variants can be more amenable to transmission fitter than others. During the course of HIV infection, the transmitted viruses evolve, presumably in response to changes in target cell population and immune response to the virus. In some but not all individuals, the virus population evolves from CCR5-tropic to CXCR4-tropic 42 ; the mechanism for this shift remains poorly understood.
Studies have shown that the sequences of transmitted HIV-1 variants resemble the ancestral viral sequences from the infecting partner rather than the contemporaneous sequences, suggesting that the virus that was first acquired in the index case is still favoured for transmission compared with later-stage viruses Viruses that are transmitted tend to have envelope proteins with less glycosylation 44 — 46 than those that are not transmitted, and some evidence suggests that transmitted viruses are less sensitive to the antiviral activities of interferons than those that are not transmitted 47 , The less-sensitive nature of transmitted viruses to interferons is of relevance given that HIV-1 induces a rapid interferon response — the virus must be able to circumvent this response to successfully establish a persistent infection 49 , Primary or acute infection.
More-severe complications — including meningitis — can occur, but many people are asymptomatic. During this period of primary or acute infection, the plasma levels of HIV RNA are typically at their peak approximately 10 6 —10 7 copies per ml.
The human immunodeficiency viruses HIV are two species of Lentivirus a subgroup of retrovirus that infect humans. Over time, they cause acquired immunodeficiency syndrome AIDS ,   a condition in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive. Research has shown for both same-sex and opposite-sex couples that HIV is untransmittable through condomless sexual intercourse if the HIV-positive partner has a consistently undetectable viral load. HIV is a member of the genus Lentivirus ,  part of the family Retroviridae. Many species are infected by lentiviruses, which are characteristically responsible for long-duration illnesses with a long incubation period. Upon entry into the target cell, the viral RNA genome is converted reverse transcribed into double-stranded DNA by a virally encoded enzyme, reverse transcriptase , that is transported along with the viral genome in the virus particle.
However, major challenges still remain. We describe basic principles of epidemic control in the context of HIV and identify a number of attainable goals in terms of control and elimination of HIV in specific populations and risk groups, given currently available HIV prevention and treatment methods. Currently available HIV prevention methods make it a feasible goal to eliminate HIV transmission attributable to mother-to-child transmission and blood transfusions. Reductions in transmission attributable to sexual behavior and injection drug use are feasible, but elimination of these modes of transmission will require further advancements in behavioral and biomedical HIV prevention. With regard to HIV-related mortality, we argue that elimination of death due to HIV-related causes is a feasible goal.
in the pathogenesis of non-AIDS clinical events (major causes of morbidity and mortality in people on antiretroviral therapy) is antiretroviral therapy.4 The global prevalence of HIV has factors Liver disease is common, mainly because of co- guidelines, including those for low-income and middle-.
All A-Z health topics. View all pages in this section. In the last 20 years, the number of pregnant women in the United States getting tested for HIV and getting preventive treatment has gone up. Today, it is possible to prevent getting an HIV infection or passing the virus to your partner or baby.
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HIV stands for human immunodeficiency virus. It harms your immune system by destroying a type of white blood cell that helps your body fight infection. This puts you at risk for serious infections and certain cancers. AIDS stands for acquired immunodeficiency syndrome.
HIV is a virus that targets and alters the immune system, increasing the risk and impact of other infections and diseases. Without treatment, the infection might progress to an advanced stage called AIDS. The life expectancy of a person with HIV is now approaching that of someone who tests negative for the virus, provided that the person takes medications called antiretroviral therapy on an ongoing basis. These are types of T cell — white blood cells that circulate, detecting infections throughout the body and faults and anomalies in other cells. HIV targets and infiltrates CD4 cells, using them to create more copies of the virus. This increases the risk and impact of opportunistic infections and some types of cancer.
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